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Updated: Sep 24, 2025
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Inflammation suppresses DLG2 expression decreasing inflammasome formation
Simon Keane1, Matthew Herring2, Peter Rolny3
1School of Health Science, DHEAR, Translational Medicine, University of Skövde, Skövde, Sweden. simon.keane@his.se.
Purpose:
Loss of expression of DLG2 has been identified in a number of cancers to contribute to the disease by resulting in increased tumor cell proliferation and poor survival. In light of the previous evidence that DLG2 alters the cell cycle and affects proliferation, combined with indications that DLG2 is involved in NLRP3 inflammasome axis we speculated that DLG2 has an immune function. So far, there is no data that clearly elucidates this role, and this study was designed to investigate DLG2 in inflammatory colon disease and in colon cancer as well as its impact on inflammasome induction.
Methods:
The DLG2 expression levels were established in publicly available inflammation, colon cancer and mouse model datasets. The overexpression and silencing of DLG2 in colon cancer cells were used to determine the effect of DLG2 expression on the activation of the inflammasome and subsequent cytokine release.
Results:
The expression of DLG2 is repressed in inflammatory colon diseases IBD and Ulcerative colitis as well as colorectal cancer tissue compared to healthy individuals. We subsequently show that induction with inflammatory agents in cell and animal models results in a biphasic alteration of DLG2 with an initial increase followed by an ensuing decrease. DLG2 overexpression leads to a significant increase in expression of IL1B, IκBζ and BAX, components that result in inflammasome formation. DLG2 silencing in THP1 cells resulted in increased release of IL-6 into the microenvironment which once used to treat bystander COLO205 cells resulted in an increase in STAT3 phosphorylation and an increase proliferating cells and more cells in the G2/M phase. Restoration of DLG2 to the colon resulted in reduced AKT and S6 signaling.
Conclusion:
DLG2 expression is altered in response to inflammation in the gut as well as colon cancer, resulting in altered ability to form inflammasomes.
Trial Registration:
NCT03072641.
Insights
DLG2 expression is reduced in inflammatory colon diseases and colon cancer, impacting inflammasome formation and cell proliferation. Restoring DLG2 function in the colon can reduce key signaling pathways involved in cancer growth.
Area of Science:
- Molecular biology
- Immunology
- Oncology
Background:
- Loss of DLG2 expression is linked to increased tumor cell proliferation and poor survival in various cancers.
- Previous research suggests DLG2 influences the cell cycle and proliferation, and may be involved in the NLRP3 inflammasome pathway.
- The precise immune function of DLG2 remains largely unelucidated.
Purpose of the Study:
- To investigate the role of DLG2 in inflammatory colon diseases and colon cancer.
- To determine the impact of DLG2 on inflammasome induction and activation.
- To explore the relationship between DLG2 expression and cellular processes like proliferation and signaling.
Main Methods:
- DLG2 expression levels were analyzed in publicly available datasets of inflammation, colon cancer, and mouse models.
- Overexpression and silencing of DLG2 were performed in colon cancer cells to assess its effect on inflammasome activation and cytokine release.
- Cell and animal models were utilized to study the dynamic changes in DLG2 expression during inflammation.
Main Results:
- DLG2 expression was found to be repressed in inflammatory colon diseases (IBD, Ulcerative Colitis) and colorectal cancer tissues compared to healthy controls.
- Inflammatory stimuli induced a biphasic alteration in DLG2 expression (initial increase followed by decrease) in cell and animal models.
- DLG2 overexpression significantly increased the expression of IL1B, IκBζ, and BAX, key components of inflammasome formation.
- DLG2 silencing in THP1 cells led to increased IL-6 release, promoting STAT3 phosphorylation and proliferation in bystander COLO205 cells.
- Restoration of DLG2 in the colon reduced AKT and S6 signaling.
Conclusions:
- DLG2 expression is significantly altered in response to gut inflammation and colon cancer.
- These alterations in DLG2 expression affect the colon's ability to form inflammasomes.
- DLG2 plays a crucial role in regulating inflammatory responses and cellular processes relevant to colon cancer development.
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